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Latest Update On The Clinical Features And Management Of Merkel Cell Carcinoma, Ahmed Nadeem Abbasi, Sumaiya Zahid

Department of Radiation Oncology

Merkel cell carcinoma (MCC), is a rare, highly malignant skin tumour, with a poor prognosis. Though the aetiology of MCC is not known, but there are several features that it shares with melanoma. These include the natural history, clinical features and behaviour, e.g. an early spread to nodal sites, high local recurrence rate and early metastasis. Incidence of MCC is seen to be increased in immunosuppressed transplant patients, in patients with rheumatoid arthritis and in B cell malignancies, with a strong male predominance. Despite the ongoing research and advancement, MCC yet poses a challenge to the clinicians because of its …

Irritable Bowel Syndrome And Psychiatric Disorders In Pakistan: A Case Control Study., Amna Subhan Butt, Mohammad Salih, Wasim Jafri, Javed Yakoob, Mohammad Wasay, Saeed Hamid

Section of Gastroenterology

Background:The psychiatric disorders like anxiety and depression could have a profound influence on onset, expression, and course of Irritable bowel syndrome (IBS). Aim: To estimate the frequency and strength of association of common mental disorders (CMDs) in Patients with IBS and Patients with other chronic diseases, that is, migraine and hypertension. Method: This was a case control study. Individuals aged 18-70 years diagnosed as IBS were enrolled as cases. The control groups consisted of Patients without IBS but diagnosed to have a chronic disease, that is, migraine or HTN. Self-Reporting Questonnaire-20(SRQ-20) was used as a screening tool for the …

Transcriptional Regulation Of N-Acetylglutamate Synthase, Sandra Kirsch Heibel, Giselle Yvette Lopez, Maria Panglao, Sonal Sodha, Leonardo Marino-Ramirez, Mendel Tuchman, Ljubica Caldovic

Pediatrics Faculty Publications

The urea cycle converts toxic ammonia to urea within the liver of mammals. At least 6 enzymes are required for ureagenesis, which correlates with dietary protein intake. The transcription of urea cycle genes is, at least in part, regulated by glucocorticoid and glucagon hormone signaling pathways. N-acetylglutamate synthase (NAGS) produces a unique cofactor, N-acetylglutamate (NAG), that is essential for the catalytic function of the first and rate-limiting enzyme of ureagenesis, carbamyl phosphate synthetase 1 (CPS1). However, despite the important role of NAGS in ammonia removal, little is known about the mechanisms of its regulation. We identified two regions of high …

A Special Issue On Dna Damage Response And Genome Stability, Guo-Min Li

Markey Cancer Center Faculty Publications

No abstract provided.

Krüppel-Like Factor 4 Regulates Intestinal Epithelial Cell Morphology And Polarity, Tianxin Yu, Xi Chen, Wen Zhang, Juan Li, Ren Xu, Timothy C Wang, Walden Ai, Chunming Liu

Markey Cancer Center Faculty Publications

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which …

Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis), Michael G. Fehlings, Alexander Vaccaro, Jefferson R. Wilson, Anoushka Singh, David W. Cadotte, James S. Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M. Massicotte, Stephen Lewis, Raja Rampersaud

Department of Neurosurgery Faculty Papers

Background: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (,24 hours after injury) versus late ($24 hours after injury) decompressive surgery after traumatic cervical SCI.

Methods: We performed a multicenter, international, prospective cohort study (Surgical Timing in Acute Spinal Cord Injury Study: STASCIS) in adults aged 16–80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was …

Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson

USF Tampa Graduate Theses and Dissertations

The RbµE2F transcriptional regulatory pathway plays a critical role in the cell cycle. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by cyclin D and cyclin E associated kinases. Once Rb is inactivated, cells can enter Sµphase. Collectively, three Rb family members and ten E2F proteins coordinate every additional stage of the cell cycle, from quiescence to mitosis. However the RbµE2F pathway is frequently altered in cancer. Aside from cell proliferation, the RbµE2F pathway regulates other essential cellular processes including apoptosis, cell differentiation, angiogenesis and DNA damage repair pathways, but its role in invasion and cancer progression is …

A Placebo-Controlled, Double-Blind, Dose-Escalation Study To Assess The Safety, Tolerability And Pharmacokinetics/Pharmacodynamics Of Single And Multiple Intravenous Infusions Of Azd9773 In Patients With Severe Sepsis And Septic Shock, Peter E. Morris, Brian Zeno, Andrew C. Bernard, Xiangning Huang, Shampa Das, Timi Edeki, Steven G. Simonson, Gordon R. Bernard

Surgery Faculty Publications

INTRODUCTION: Tumor necrosis factor-alpha (TNF-α), an early mediator in the systemic inflammatory response to infection, is a potential therapeutic target in sepsis. The primary objective of this study was to determine the safety and tolerability of AZD9773, an ovine, polyclonal, anti-human TNF-α Fab preparation, in patients with severe sepsis. Secondary outcomes related to pharmacokinetic (PK) and pharmacodynamic (PD) parameters.

METHODS: In this double-blind, placebo-controlled, multicenter Phase IIa study, patients were sequentially enrolled into five escalating-dose cohorts (single doses of 50 or 250 units/kg; multiple doses of 250 units/kg loading and 50 units/kg maintenance, 500 units/kg loading and 100 units/kg maintenance, …

Loss Of Αt-Catenin Alters The Hybrid Adhering Junctions In The Heart And Leads To Dilated Cardiomyopathy And Ventricular Arrhythmia Following Acute Ischemia., Jifen Li, Steven Goossens, Jolanda Van Hengel, Erhe Gao, Lan Cheng, Koen Tyberghein, Xiying Shang, Riet De Rycke, Frans Van Roy, Glenn L Radice

Center for Translational Medicine Faculty Papers

It is generally accepted that the intercalated disc (ICD) required for mechano-electrical coupling in the heart consists of three distinct junctional complexes: adherens junctions, desmosomes and gap junctions. However, recent morphological and molecular data indicate a mixing of adherens junctional and desmosomal components, resulting in a 'hybrid adhering junction' or 'area composita'. The α-catenin family member αT-catenin, part of the N-cadherin-catenin adhesion complex in the heart, is the only α-catenin that interacts with the desmosomal protein plakophilin-2 (PKP2). Thus, it has been postulated that αT-catenin might serve as a molecular integrator of the two adhesion complexes in the area composita. …

Neuroscience Of Personality: Principles Of The Psyche As A Living System, Dario Nardi

Systems Science Friday Noon Seminar Series

The brain is a complex living system. Using colorful slides and anecdotes, Dario Nardi, PhD will overview his hands-on research of the past 5 years in his social neuroscience lab using EEG technology to better understand the neocortex. He spends 2 to 3 hours with each subject, offering a variety of tasks from solo activities like meditating, drawing, and recalling to social activities like poker and speed-dating. The results are in. The neocortex relies upon a dynamic of modules, circuits, and holistic modes to continuously coordinate with the environment in both a top-down and a bottom-up manner. Moreover, individual differences …

Lithium Treatment Of Appswdi/Nos2−/− Mice Leads To Reduced Hyperphosphorylated Tau, Increased Amyloid Deposition And Altered Inflammatory Phenotype, Tiffany L. Sudduth, Joan G. Wilson, Angela Everhart, Carol A. Colton, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2-/- mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2-/- mice for a period of eight months, followed by water maze …

Integrating Spiritual Care Within Palliative Care: An Overview Of Nine Demonstration Projects, Shirley Otis-Green, Betty Ferrell, Tami Borneman, Christina Puchalski, Gwen Uman, Andrea Garcia

Medicine Faculty Publications

No abstract provided.

The Expression Of Ecotropic Virus Integration Site-1 In Seven Cancer Cell Lines, Wendy Bindeman '12

Student Publications & Research

The ecotropic virus integration site-1 (EVI1) gene is a transcriptional repressor implicated in the control of cell proliferation and frequently over-expressed in cancerous cells. I investigated the expression of this gene across seven cancer cell lines of varying morphologies. The tested lines included leukemia lines Kasumi-3, U937, MOLT-4, and CEM, breast cancer line MCF7, colorectal cancer line HT-29, and glioblastoma line M059K. Kasumi-3 and HT-29 are documented to have high EVI1 expression. Protein concentrations were normalized with respect to actin using SDS-PAGE and Western blotting. Western blots for EVI1 showed expression of an unidentified protein with a molecular weight of …

The Evidence-Based Pharmacological Treatment Of Paediatric Adhd., Brigette S. Vaughan, John S. March, Christopher J. Kratochvil

Journal Articles: Psychiatry

Attention deficit hyperactivity disorder (ADHD) is common in children, adolescents, and adults, with extensive research establishing it as a valid neurobiological disorder. Without intervention, ADHD can result in significant impairment throughout the lifespan for the individuals it afflicts. Fortunately, multiple evidence-based options are available for the treatment of ADHD, including several efficacious pharmacotherapies. The role of medication, including stimulants as well as non-stimulants, is well-documented by an extensive body of literature. Although there may be less enthusiasm for behavioural and other psychosocial interventions as stand-alone treatments for moderate to severe ADHD, they are recommended as first-line treatment for ADHD management …

Oncolog, Volume 57, Number 02, February 2012, Don Norwood, Bryan Tutt

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Pediatric and Adult Cancer Patients Face Different Issues in Care, Survivorship: The challenges faced by children and adults with cancer can differ markedly, even when they have the same type of cancer
• Palliative Care May Offer Survival Benefits: Recent studies indicate that palliative care, which has been shown to improve quality of life in patients with advanced cancer, may also help patients live longer
• INBRIEF: Targeted Therapy Causes Chronic Lymphocytic Leukemia Remission/Study Finds Acupuncture Can Prevent Radiation-Induced Chronic Dry Mouth
• HOUSE CALL: Understanding the risks, benefits, and purpose of a trial can help cancer patients decide whether to participate

Functional, Cognitive And Psychological Outcomes, And Recurrent Vascular Events In Pakistani Stroke Survivors: A Cross Sectional Study., Maria Khan, Bilal Ahmed, Maryam Ahmed, Myda Najeeb, Emmon Raza, Farid Khan, Anoosh Moin, Dania Shujaat, Ahmed Arshad, Ayeesha Kamran Kamal

Department of Medicine

Background: There is little direct data describing the outcomes and recurrent vascular morbidity and mortality of stroke survivors from low and middle income countries like Pakistan. This study describes functional, cognitive and vascular morbidity and mortality of Pakistani stroke survivors discharged from a dedicated stroke center within a nonprofit tertiary care hospital based in a multiethnic city with a population of more than 20 million.

Methods: Patients with stroke, aged > 18 years, discharged alive from a tertiary care centre were contacted via telephone and a cross sectional study was conducted. All the discharges were contacted. Patients or their legal surrogate …

Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin …

Acute Myeloid Leukaemia In Children: Experience At A Tertiary Care Facility Of Pakistan, Zehra Fadoo, Naureen Mushtaq, Saima Alvi, Muhammad Ali

Department of Paediatrics and Child Health

Objective: To document the demographics and outcome of children with Acute Myeloid Leukemia (AML) treated at a tertiary care facility of Pakistan.

Methods: A retrospective study was conducted at Aga Khan University on children (less than 15 years) diagnosed to have AML between January 2000 to May 2007.Total 40 cases were diagnosed out of which 37 charts were available for review.

Results: The average age of presentation was 8.5±4.5 years and 75% were males. The most common presenting feature was fever in 83% followed by bleeding in 41% and pallor in 39%. Initial WBC of > 100,000 was seen in 19% …

Current Methodological Issues In Candidate Gene Association Studies In Psychiatric Disorders, Leo Sher M.D.

Jefferson Journal of Psychiatry

One of the most rapidly emerging areas of neuroscience research is the study of genetic approaches to complex psychiatric disorders. The author discusses potential benefits and pitfalls of candidate gene association studies. Association studies search for correlations in the population between a DNA marker and a disorder. The so-called candidate gene approach is frequently used in association studies. Candidate gene studies are usually based on hypotheses about relationships between specific known loci and particular phenotypes. The aim of molecular genetic studies of behavioral disorders includes the development of predictive and diagnostic testing for psychiatric disorders that can help to establish …

Mechanisms Of Fetal Programming In Hypertension., John E. Jones, Julie A. Jurgens, Sarah A. Evans, Riley C. Ennis, Van Anthony Villar, Pedro A. Jose

Pediatrics Faculty Publications

Events that occur in the early fetal environment have been linked to long-term health and lifespan consequences in the adult. Intrauterine growth restriction (IUGR), which may occur as a result of nutrient insufficiency, exposure to hormones, or disruptions in placental structure or function, may induce the fetus to alter its developmental program in order to adapt to the new conditions. IUGR may result in a decrease in the expression of genes that are responsible for nephrogenesis as nutrients are rerouted to the development of more essential organs. Fetal survival under these conditions often results in low birth weight and a …

Glenohumeral Tuberculous Arthritis Complicated With Beta Haemolytic Streptococcus: An Extraordinary Rare Association: A Case Report, Rizwan Haroon Rashid, Muhammad Usman Sarwar, Jaweed Akhter, Shahryar Noordin

Section of Orthopaedic Surgery

Introduction: Septic arthritis of the glenohumeral joint is a rare entity and its diagnosis is difficult with a superadded infection in the presence of underlying tuberculosis. We report the first case of group B beta haemolytic streptococcal glenohumeral arthritis with underlying tuberculosis.
Case Presentation: A 40 year old lady previously diagnosed to have poliomyelitis, rheumatoid arthritis, hepatitis C, and diabetes mellitus for the last 10 years, presented to the emergency room with diabetic ketoacidosis. Two weeks prior to presentation she developed fever along with pain and swelling in left shoulder with uncontrolled blood sugars. Local examination of the shoulder revealed …

Personality Traits In Juvenile Delinquents: Associations With Peer And Family Relations, Jeffrey J. Wilson M.D., Sharon E. Willams Ph.D., Evan Garner M.D., Elaine Duxbury B.A., Hans Steiner Dr. Med. Univ.

Jefferson Journal of Psychiatry

Objective: To establish family and peer correlates of personality traits shown to be predictive of future criminal recidivism.

Method: 137 incarcerated boys aged 13-18 (x = 16 ± 1.2), 35% black, 21% Hispanic, 43% white, and 1% other completed the Weinberger Adjustment Inventory (WAI) and a psychosocial history obtained by a social worker. Records were summarized using two raters who assigned numerical ratings to dimensions of family and peer relations.

Results: As expected, observer ratings of family and peer relationships were correlated with the personality characteristics of distress, denial and restraint as measured by the WAI.

Conclusion: Family and peer …

Countertransference In Two Settings: A Case Report, Randi L. Plotkin M.D.

Jefferson Journal of Psychiatry

No abstract provided.

Conversion Disorder In A Depressed Patient: The Analysis Of Paralysis, Michael A. Chen Ph.D., David S. Im M.D.

Jefferson Journal of Psychiatry

Patients presenting with neurologic and pseudoneurologic symptoms present both a diagnostic and treatment challenge. This case report describes the ER course of a man who presented with aphonia and paralysis, his medical clearance, transfer to the psychiatric ER and subsequent recovery. The history of conversion disorder and its characteristics are briefly reviewed, and the etiology of this patient's symptoms and a discussion of effective treatment plans are discussed.

About The Authors

Jefferson Journal of Psychiatry

No abstract provided.

Seasonal Affective Disorder And Seasonality: A Review, Leo Sher M.D.

Jefferson Journal of Psychiatry

Seasonal affective disorder is a condition where depressions in fall and winter alternate with nondepressed periods in the spring and summer. The Degree to which seasonal changes affect mood, energy, sleep, appetite, food preference, or the wish to socialize with other people has been called "seasonality." The author reviews historical aspects, clinical features, epidemiology, genetics, pathophysiology, and treatment of seasonal affective disorder and seasonality. Better understanding of the contemporary concept of seasonal affective disorder, seasonality, and light treatment will improve patient care and promote scientific advances in behavioral sciences.

Case Report Of Dramatic Resolution Of Psychotic Symptoms During Cross-Over To Clozapine, Leo Sher M.D., Alan Mendelowitz M.D.

Jefferson Journal of Psychiatry

Clozapine is the first antipsychotic drug with proven superiority over conventional antipsychotics in the management of treatment-resistant patients. We describe a case of tratment-resistant schizoaffective disorder in a young woman who improved rapidly on clozapine. The patient was started on a low dose of clozapine while fluphenazine was decreased. She improved significantly during the first several days of treatment. This improvement took place well before the expected effect of clozapine. Possible explanations for this unusual response include: 1) the placebo effect; 2) fluphenazine dose-response curve; 3) acute clozapine neurochemical mechanisms; 4) inaccurate original diagnosis. Better understanding of the mechanisms of …

Case Report: Failure Of Group Therapy With Elderly Russian-Jewish Immigrants (An Exploratory Analysis), Gennady Berezkin M.D.

Jefferson Journal of Psychiatry

This paper is a description of an unsuccessful attempt to carry out group therapy with elderly Russian-Jewish immigrants.

An attempt was made to conduct group therapy following general principals of traditional psychotherapy with geriatric populations.

In the final analysis, we conclude that culturally based preconceptions toward psychotherapy, culturally based stereotypes of interpersonal relationships and culturally-based transference to the therapist were the primary reasons for the development of negative transference and resistance which culminated in the ultimate failure of group psychotherapy with this group of elderly immigrants.

Inflammatory Signaling Compromises Cell Responses To Interferon Alpha., W-C Huangfu, J Qian, C Liu, J Liu, A E Lokshin, D P Baker, H Rui, S Y Fuchs

Department of Cancer Biology Faculty Papers

Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNβ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here, we report that inflammatory signaling impedes the effects of IFNα/β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/β signaling induced by proinflammatory …

The Relevance Of Transference During Medication Management: A Case Of Erotized Transference, Helen C. Kales M.D., James Abelson M.D., Ph.D., Michelle B. Riba M.D.

Jefferson Journal of Psychiatry

Forces existing in psychiatry may diminish the importance of psychotherapy training as psychiatrists are increasingly given the task of medication management. Psychotherapeutic relationships can be created in medication management settings, however, and the neglect of concepts such as transference could have deleterious consequences. The authors describe the case of a man with a traumatic brain injury referred for medication management who developed an erotized transference toward his female resident-physician. This case illustrates the concept that an understanding of transference is relevant to the setting of medication management